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dc.contributor.authorRchiad, ‍Zineb
dc.contributor.authorHaidar, Malak
dc.contributor.authorAnsari, Hifzur Rahman
dc.contributor.authorTajeri, Shahin
dc.contributor.authorBen Rached, Fathia
dc.contributor.authorLangsley, Gordon
dc.contributor.authorPain, Arnab
dc.date.accessioned2018-09-03T13:24:55Z
dc.date.available2018-09-03T13:24:55Z
dc.date.issued2018-06-05
dc.identifier.citationRchiad Z, Haidar M, Ansari HR, Tajeri S, Ben Rached F, et al. (2018) GZMA and RASGRP1 are novel tumor suppressors that counter dissemination of Theileria annulata-transformed macrophages. Available: http://dx.doi.org/10.1101/338160.
dc.identifier.doi10.1101/338160
dc.identifier.urihttp://hdl.handle.net/10754/628453
dc.description.abstractTheileria annulata is a tick-transmitted apicomplexan parasite that infects and transforms bovine leukocytes into disseminating tumors that cause a disease called tropical theileriosis. Using RNA sequencing we identified bovine genes, whose transcription is perturbed during Theileria-induced transformation to define the transcriptional atlas of transformed virulent versus attenuated (dampened dissemination) macrophages and transformed B cells. Dataset comparisons highlighted a small set of novel genes associated with Theileria-transformed leukocyte dissemination and the roles of Granzyme A (GZMA) and RAS guanyl-releasing protein 1 (RASGRP1) confirmed by CRISPR/Cas9-mediated down-regulation of their expression. Knockdown of both GZMA and RASGRP1 in attenuated macrophages led to a regain in their dissemination in Rag2/γC mice confirming in vivo both GZMA and RASGRP1 as novel dissemination suppressors.
dc.description.sponsorshipThis study was supported by the Competitive Research Grant 4 (OSR-2015-CRG4-2610) from the Office for Sponsored Research in King Abdullah University of Science and Technology (KAUST). ST was supported by a ParaFrap postdoctoral fellowship and GL acknowledges support from Labex ParaFrap (ANR-11-LABX-0024), INSERM and the CNRS.
dc.publisherCold Spring Harbor Laboratory
dc.relation.urlhttps://www.biorxiv.org/content/early/2018/06/04/338160
dc.rightsThe copyright holder for this preprint is the author/funder. It is made available under a CC-BY-NC-ND 4.0 International license.
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectTheileria annulata
dc.subjectTransformation
dc.subjectTranscriptome
dc.subjectDissemination
dc.subjectRASGRP1
dc.subjectGZMA
dc.subjectTumor suppressor
dc.titleGZMA and RASGRP1 are novel tumor suppressors that counter dissemination of Theileria annulata-transformed macrophages
dc.typePreprint
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Division
dc.contributor.departmentBioscience Program
dc.contributor.departmentComputational Bioscience Research Center (CBRC)
dc.contributor.departmentPathogen Genomics Laboratory
dc.eprint.versionPre-print
dc.contributor.institutionLaboratoire de Biologie Cellulaire Comparative des Apicomplexes, Faculté de Médecine, Université Paris Descartes - Sorbonne Paris Cité, France.
dc.contributor.institutionInserm U1016, Cnrs UMR8104, Cochin Institute, Paris, 75014 France.
dc.contributor.institutionKing Abdullah International Medical Research Center (KAIMRC), King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Jeddah 21423, Saudi Arabia.
dc.contributor.institutionGlobal Station for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, N20 W10 Kita-ku, Sapporo, Japan.
kaust.personRchiad, ‍Zineb
kaust.personHaidar, Malak
kaust.personAnsari, Hifzur Rahman
kaust.personBen Rached, Fathia
kaust.personPain, Arnab
kaust.grant.numberOSR-2015-CRG4-2610
refterms.dateFOA2018-09-05T12:56:27Z


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The copyright holder for this preprint is the author/funder. It is made available under a CC-BY-NC-ND 4.0 International license.
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